The goal of the Mount Sinai program project on Cellular and Molecular Markers in Schizophrenia is to elucidate the genetic, cellular and molecular substrates underlying schizophrenia. A multidiciplinary approach using sophisticated neurobiological approaches is adopted in the form of 4 cores and 8 research projects. The cores provide the infrastructure for resource sharing. The administrative Core Orchestrates the interdigitation of the projects, and provides biostatistical support and an efficient administrative base. The Recruitment/ Assessment/Neuropathology Core provides thoroughly characterized tissues from patients and controls with objective antemortem diagnosis for use by the projects. The Family Study Core identifies and characteristics probands and relatives for linkage and segregation analyses (Project 1). Virtually all of the projects use the resources of the MOlecular Biology Core which procures, characterizes, banks, and disseminates human brain RNA, and performs the specialized in situ hybridization studies required by 4 of the 8 studies. At a cellular level, projects headed by Dr. Benes (Project 3) and Dr. Morrison (Project 2) aim not only to identify and study structural abnormalities associated with schizophrenia, but also the characterize the cellular organization of the human and primate pre- and postsynaptic dopaminergic system and to investigate the possible involvement of glutaminergic and GABAergic interneuronal systems. The biosynthetic mechanisms of the dopaminergic system will be studied with respect to the regulation and differential processing of tyrosine hydroxylase mRNAs in normal and schizophrenic tissues (Project 4). At a postsynaptic level, the role of the dopamine D2 receptor and its possible subtypes in schizophrenia will be investigated by first characterizing the structure of the gene(s) encoding them and then studying their expression in schizophrenic and control tissue (Project 5). The mechanisms and manner of regulation of these same receptors will be investigated in the rodent brain, where the effects of clinically relevant neuroleptics will be assessed (Project 6). To gain a deeper understanding of dopamine receptor function and the role of CCK, the CCK receptor will be cloned (Project 8) and dopamine D2 and CCK receptor structure and function relationships and interactions will be studied electrophysiologically in an oocyte expression system (Project 7).